Different Types, Different Fights!

• A "too-late" diagnosis is the first reason why some cancers are difficult to treat.
• The pancreas and esophagus are hidden behind other organs, and their respective tumors are hard to spot.
• Small-cell lung cancer cells spread very quickly outside the lungs (metastasize).
• A low immune response from "cold tumors" is the second reason.
• Researchers classify tumors as hot or cold.
• "Hot" tumors (e.g., melanoma) produce unusual antigens that the T-cells (i.e., immune-defense cells) can more easily recognize and attack.
• "Cold" tumors (e.g., pancreatic cancer) don't express antigens, therefore cause a low immune response and make checkpoint inhibitors (currently the most promising development in immuno-oncology) way less effective.
• The key is to turn "cold tumors" into "hot tumors" through new immunooncology strategies that stimulate the immune response and make checkpoint inhibitors effective again.

Combining Immuno-oncology Strategies With Checkpoint Inhibitors

Targeted Therapies: The Hope To Beat ALL cancers! 

• With hard-to-treat cancers, a key issue is early detection: once the disease spreads to other organs, it is often too late. Understanding how different types of cancer cells grow and spread across the body is essential.
• Improvement of diagnosis tools (genetic tests) will increase the number of patients diagnosed in difficult-to-treat cancers.
• Targeted therapies identify and target tumor-specific genetic mutations.
• Mutations in a gene called KRAS characterize some pancreatic and esophageal cancers subtypes. The mutated gene sends signals that lead to abnormal cell division. Mirati Therapeutics (MRTX US), Amgen (AMGN US), and Novartis (NOVN SW) have compounds inhibiting KRAS mutated gene.
• The TP53 mutated gene is vastly present in pancreatic, small cell lung, ovarian, breast and esophageal cancers. Aprea Therapeutics (APRE US), which did its IPO in of October 2019, targets the P53 protein.
• Hard-to-treat cancers with specific genetic mutations will benefit from the development of “tissue agnostic” treatments (based on a common gene mutation across different tumors rather than the primary location). Larotrectinib, developed by Loxo Oncology (acquired by Elli Lily (LLY US)) was approved in 2018 for several indications, including difficult cancers.

Catalysts:

• A top priority. Due to high medical need, hard-to-treat cancers benefit from a strong inflow of financial resources.
• A better diagnosis. The mapping of difficult-to-treat cancer genes associated with genetic tests will help to identify new drugs targets and increase the number of diagnosed patients.
• High M&A activity. To enhance the efficacy of treatments on these types of cancers, the best approach is combination therapies between innovative and existing drugs. The need to collaborate between companies leads to more M&A and partnerships.
• Adaptive trials. New oncology clinical trials are designed to adapt to improved understanding of cancer genetics and could extend existing indications to hard-to-treat cancers.
• In basket trials, for example, drugs are being evaluated on cancers that have a similar genetic mutation rather than the same location.

Risks:

• Plenty of innovative but uncertain approaches. Trials could be stopped due to unpredictable clinical outcomes.
• Difficult patient recruitment. During clinical trials, patients retention is complicated by the low survival rates in these types of cancers.
• A competitive therapeutic area. The oncology field is a crowded space with many compounds currently in development.